TY - JOUR T1 - A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules A1 - Jilkine, Alexandra A1 - Angenent, Sigurd B. A1 - Wu, Lani F. A1 - Altschuler, Steven J. Y1 - 2011/11/10 N2 - Author Summary A large body of work has focused on the ability of positive feedback in biological networks to create either switches in time (i.e., cells are either in an “on” or an “off” state) or form patterns in space (i.e., spatial organization in cells and tissues). Here, we propose a stochastic “neutral drift polarity model” by which positive feedback alone is sufficient to create switch-like behaviors both in time and space for finite molecule numbers. Our theory predicts that below a critical density of signaling molecules, positive feedback robustly maintains an off state; exceeding this threshold switches on the recurrent emergence of highly localized signaling clusters. Cluster formation requires only this minimal positive feedback circuit, and does not require additional mechanisms such as diffusion barriers, spatial cues, or biochemical inhibitors. This mechanism is general, and could be applied to a variety of cellular signaling systems to create clusters in the membrane, cytosol, or organelles. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 7 IS - 11 UR - https://doi.org/10.1371/journal.pcbi.1002271 SP - e1002271 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002271 ER -